1. Field of the Invention
This invention belongs to the field of synthetic organic chemistry, and provides a process for the synthesis of esters of phenylacetic acids in a single step from 2,2,2-trichloro-1-phenylethanes.
2. State of the Art
The hydrolysis of trichloromethyl compounds to form carboxylic acids and derivatives thereof is well known. For example, Belgian Pat. No. 760,968 shows the formation of 3-trifluoromethylphenylacetic acid from the corresponding 2,2,2-trichloroethane by hydrolysis with potassium hydroxide in ethylene glycol. Dombrovskii and Naidan, J. Org. Chem. U.S.S.R. 32, 1256-58 (1962), prepared phenylacetic acid by hydrolyzing 2,2,2-trichloro-1-phenylethane with lead nitrate in acetic acid, and the same authors, J. Org. Chem. U.S.S.R. 34, 1474-77 (1964), prepared phenylacetic acid and 4-nitrophenylacetic acid by hydrolyses with mercuric oxide, or with sulfuric acid.
Various trichloromethylbenzene compounds have been hydrolyzed to the corresponding acid chlorides, for example with ferric chloride and with siloxanes. Hill, J. Org. Chem. 25, 1115-18 (1960), and Nakamo et al., J. Chem. Soc. Chem. Comm., 808-09 (1977).
Other aryltrichloromethyl compounds have been hydrolyzed to the corresponding acids with perchloric acid in acetic acid, and cuprous chloride in hydrochloric acid. Cadogan and Duell, J. Chem. Soc., 4154-57 (1962); Kharasch et al., J. Org. Chem. 18, 328-32 (1953); Kharasch et al., J. Am. Chem. Soc. 69, 1100-05 (1947).
There is some precedent in the literature for the formation of carboxylic acid esters from trichloromethane compounds. One system proceeds by reactions with sodium alkoxides, as taught by Hilgetag and Martini, Preparative Organic Chemistry, John Wiley and Sons, New York, 1972, page 341; Wakselman and Molines, Synthesis 622-23 (1979); and Kharasch et al., J. Am. Chem. Soc. 69, 1105 (1947). The process is acceptable with alkyl compounds, but is not satisfactory for phenylethane derivatives.
Esters have also been prepared by a process which proceeds through ortho-ester intermediates, as shown by Kimoto and Cohen, J. Org. Chem. 45, 3831-35 (1980), who worked with 2-trifluoromethylimidazoles and converted them to the corresponding 2-(carbomethoxy)imidazoles, proceeding through the trimethoxymethane intermediate, and Hill et al., J. Org. Chem. 30, 411-15 (1965), who converted benzotrichlorides to orthobenzoates with metal halides such as aluminum chloride and ferric chloride. The phenylethanes which are starting compounds of the present invention are inert to these conditions; the imidazole starting compounds of Kimoto, in particular, are quite unique because of the tautomerism of their double bonds.
Finally, Smith et al., Synthesis 493-95 (1980), prepared the t-butyl ester of a complexly substituted pyrrole-2-carboxylic acid by reacting the corresponding 2-trichloromethylpyrrole with t-butanol and sodium acetate.